No Link Between Autism and Flu Vaccination During Pregnancy

Lara C. Pullen, PhD

November 30, 2016

Neither influenza infection nor influenza vaccination during pregnancy increase the risk for autism, according to a new study published online November 28 in JAMA Pediatrics.

That said, the data showed a nonsignificant trend for increased risk for autism spectrum disorder (ASD) among offspring of mothers who received an influenza vaccination during their first trimester. Although the findings could be a result of chance, the investigators call for additional studies on the relationship between maternal influenza vaccination and autism.

Ousseny Zerbo, PhD, a postdoctoral researcher at Kaiser Permanente in Oakland, California, and colleagues analyzed data from a large birth cohort (n = 196,929) of children born at Kaiser Permanente between January 1, 2000, and December 31, 2010. The children had a gestational age of 24 weeks or older.

The investigators used prospectively collected information from medical records that documented maternal influenza infection and influenza vaccination during pregnancy and ASD diagnosis among the offspring. This approach allowed the researchers to evaluate risk associated with infection and vaccination during specific periods of pregnancy, as well as adjust for important covariates.

Influenza Shots Are Recommended for Pregnant Women

At this time, the Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for pregnant women.

"The risk of damage to the fetus and severe morbidity (and even death) to the pregnant mother as a result of infection is great, and as a result, recommendations from bodies such as the [World Health Organization] and the ACIP strongly urge that pregnant women be vaccinated against influenza," explained Litjen Tan, PhD, chief strategy officer of the Immunization Action Coalition, to Medscape Medical News.

"However, there remains uncertainty as to whether maternal infection with influenza results in an increased risk of ASD in the child. Specifically, since both influenza infection and vaccination can yield a transient inflammatory response, it was important to discover whether either would result in increased ASD risk."

Overall, 0.7% of the mothers were diagnosed with influenza during pregnancy, but the data show no elevation in ASD risk among the children (adjusted hazard ratio [aHR], 1.04; 95% confidence interval [CI], 0.68 - 1.58). Although the investigators acknowledge that diagnosis of infection could be affected by disease severity, mother's health care access, and care-seeking behavior, they report that not only was influenza infection not associated with ASD, but the timing of influenza infection during pregnancy did not affect the risk for ASD.

Approximately one quarter (23%) of pregnant women in the cohort received influenza vaccination. Although vaccination throughout pregnancy was not associated with an increased ASD risk (aHR, 1.10; 95% CI, 1.00 - 1.21), vaccination during the first trimester was associated with a slightly increased ASD risk (aHR, 1.20; 95% confidence interval, 1.04 - 1.39; P = .1).

"We found that influenza vaccination in the first trimester was associated, in an initial analysis unadjusted for multiple comparisons, with a slightly increased ASD risk after controlling for maternal allergy, asthma, autoimmune conditions, gestational diabetes, hypertension, age, education, race/ethnicity, child conception year, conception season, sex, and gestational age," the authors write. "However, adjusting for the multiplicity of hypotheses tested suggests that the results could be due to chance. If influenza vaccination during the first trimester of pregnancy causes ASD, our results suggest that it would amount to four additional ASD cases for every 1000 women vaccinated."

Dr Tan found the results reassuring. "Even the most surprising finding — that after adjustment of covariates, influenza vaccination in the first trimester appeared to be associated with a slightly increased ASD risk — was likely a chance occurrence after the authors performed a Bonferroni correction to counteract the problem of multiple comparisons/covariates present in this study's design," he explained. "This would seem to be supported by the lack of increased risk when vaccine was given during the second and third trimester."

One of the authors has received research grant support from GlaxoSmithKline, Sanofi Pasteur, Merck, Pfizer, Protein Science, MedImmune, and Novartis. Dr Tan is employed by the Immunization Action Coalition, which receives funding from the Centers for Disease Control and Prevention and commercial vaccine manufacturers.

JAMA Pediatr. Published online November 28, 2016. Full text

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